α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

Abstract

Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, α-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. α-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with α-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas α-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in α-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both α-mangostin and apigenin arrested the cell cycle at the G 2 /M phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and α-mangostin-treated SKOV-3 cells, respectively. α-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and α-mangostin likely being involved with inflammation.

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

“…T h e v i a b i l i t y o f t h e c e l l s w a s a s s e s s e d b y 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetra-zolium bromide (MTT) assay, as previously described (37). Briefly, T24 cells were seeded onto 96-well plates at a agarose gels containing 0.1 μg/mL ethidium bromide (EtBr, Sigma-Aldrich Chemical Co.).…”

Ethanol Extract of Hizikia fusiforme Induces Apoptosis in B16F10 Mouse Melanoma Cells through ROS-Dependent Inhibition of the PI3K/Akt Signaling Pathway

“…B16F10 cells purchased from the American Type Culture Collection (Manassas, MD, USA) were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin (all from WelGENE Inc., Daegu, Republic of Korea) at 37°C in 5% CO 2 humidified incubator. The cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5diphenyltetrazolium bromide (MTT) assay, as previously described (Ittiudomrak et al, 2019). In brief, B16F10 cells were seeded onto 96-well plates at a density of 1×10 4 cells/ well.…”

Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation

“…For apoptosis analysis, cells were harvested and suspended in 100 µL of phosphate-buffered saline, and added to 200 µL of 95% ethanol [36]. And then, cells were incubated in 1.12% sodium citrate buffer containing RNase at 37 • C for 30 min, added to 50 µg/mL propidium iodide, and analyzed using BD Accuri™ C6 flow cytometer (BD Biosciences, San Jose, CA, USA).…”